Rob Feltz, Director, Analytical and Formulation Services, talks about techniques that reduce particle size.

A few weeks ago, I wrote about several formulation techniques that increase particle size, including roller compaction, high-shear granulation, and fluid-bed granulation.

Today, let’s talk about techniques that reduce particle size.
But first, let’s refresh our knowledge of particle size and why it’s important.

As particle size decreases, the surface area to volume ratio increases. This larger relative surface area enhances the dissolution rate and solubility of the particles, which can lead to improved bioavailability, especially for poorly soluble drugs.

Smaller particles are generally more easily absorbed through biological membranes in the GI tract. They can also penetrate tissues more effectively, potentially improving distribution throughout the body.

Particle size can also affect the stability of the drug. ๐—ฆ๐—บ๐—ฎ๐—น๐—น๐—ฒ๐—ฟ ๐—ฝ๐—ฎ๐—ฟ๐˜๐—ถ๐—ฐ๐—น๐—ฒ ๐˜€๐—ถ๐˜‡๐—ฒ ๐—น๐—ฒ๐—ฎ๐—ฑ๐˜€ ๐˜๐—ผ ๐—น๐—ฎ๐—ฟ๐—ด๐—ฒ๐—ฟ ๐˜€๐˜‚๐—ฟ๐—ณ๐—ฎ๐—ฐ๐—ฒ ๐—ฎ๐—ฟ๐—ฒ๐—ฎ, ๐˜„๐—ต๐—ถ๐—ฐ๐—ต ๐—บ๐—ฒ๐—ฎ๐—ป๐˜€ ๐—ถ๐—ป๐—ฐ๐—ฟ๐—ฒ๐—ฎ๐˜€๐—ฒ๐—ฑ ๐—ฝ๐—ผ๐˜๐—ฒ๐—ป๐˜๐—ถ๐—ฎ๐—น ๐—ณ๐—ผ๐—ฟ ๐—ฟ๐—ฒ๐—ฎ๐—ฐ๐˜๐—ถ๐˜ƒ๐—ถ๐˜๐˜† ๐˜„๐—ถ๐˜๐—ต ๐—ฑ๐—ผ๐˜„๐—ป๐˜€๐˜๐—ฟ๐—ฒ๐—ฎ๐—บ ๐—ถ๐—บ๐—ฝ๐—น๐—ถ๐—ฐ๐—ฎ๐˜๐—ถ๐—ผ๐—ป๐˜€ ๐—ผ๐—ป ๐—ฐ๐—ต๐—ฒ๐—บ๐—ถ๐—ฐ๐—ฎ๐—น (๐—ถ๐—ป)๐˜€๐˜๐—ฎ๐—ฏ๐—ถ๐—น๐—ถ๐˜๐˜†.

During particle size-reduction, mechanical energy is imparted from the mill to the material in order to break it into smaller particles. The four most commonly used size reduction mechanisms are:

  • Compression
  • Cutting
  • Impact
  • Attrition

๐—–๐—ผ๐—บ๐—ฝ๐—ฟ๐—ฒ๐˜€๐˜€๐—ถ๐—ผ๐—ป is used for coarse reduction of large particles but is less effective for soft, elastic materials. It can also be difficult to achieve very fine particles sizes with this technique. Examples are roller mills and some conical mills.

๐—–๐˜‚๐˜๐˜๐—ถ๐—ป๐—ด the particle size involves using sharp edges to shear the material as opposed to crushing or grinding. This method is good for elastic materials but poor for hard or brittle materials. May also be difficult to be achieve fine particle sizes. Examples: knife mills and some granulators.

๐—œ๐—บ๐—ฝ๐—ฎ๐—ฐ๐˜ ๐—บ๐—ถ๐—น๐—น๐—ถ๐—ป๐—ด reduces particle size by subjecting the material to high-speed hammers or similar tools. These mills are highly efficient but produce a wide distribution of particle sizes, so they may not be appropriate for some applications. Examples: hammer mills, jet mills.

๐—”๐˜๐˜๐—ฟ๐—ถ๐˜๐—ถ๐—ผ๐—ป is a method that involves grinding and shearing particles against each other or a solid surface. It is suitable for creating fine and uniform particles but not for coarse size reduction. Examples are granulators and planetary mills.

To bring it all together, a well-controlled particle size is critical to consistent bioavailability of certain products. Learn this information to understand the advantages and limitations of your mill.

You can read more from Rob by following him on LinkedIn.